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GeneBe

14-89162657-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005197.4(FOXN3):c.1164G>T(p.Gly388=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,613,962 control chromosomes in the GnomAD database, including 130 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0082 ( 12 hom., cov: 31)
Exomes 𝑓: 0.010 ( 118 hom. )

Consequence

FOXN3
NM_005197.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.713
Variant links:
Genes affected
FOXN3 (HGNC:1928): (forkhead box N3) This gene is a member of the forkhead/winged helix transcription factor family. Checkpoints are eukaryotic DNA damage-inducible cell cycle arrests at G1 and G2. Checkpoint suppressor 1 suppresses multiple yeast checkpoint mutations including mec1, rad9, rad53 and dun1 by activating a MEC1-independent checkpoint pathway. Alternative splicing is observed at the locus, resulting in distinct isoforms. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-89162657-C-A is Benign according to our data. Variant chr14-89162657-C-A is described in ClinVar as [Benign]. Clinvar id is 2644444.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.713 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1247 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXN3NM_005197.4 linkuse as main transcriptc.1164G>T p.Gly388= synonymous_variant 6/6 ENST00000557258.6
FOXN3NM_001085471.2 linkuse as main transcriptc.1230G>T p.Gly410= synonymous_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXN3ENST00000557258.6 linkuse as main transcriptc.1164G>T p.Gly388= synonymous_variant 6/61 NM_005197.4 A1O00409-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00821
AC:
1247
AN:
151960
Hom.:
12
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00164
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00190
Gnomad ASJ
AF:
0.00260
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000209
Gnomad FIN
AF:
0.0221
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0132
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00758
AC:
1895
AN:
250000
Hom.:
16
AF XY:
0.00741
AC XY:
1002
AN XY:
135234
show subpopulations
Gnomad AFR exome
AF:
0.00209
Gnomad AMR exome
AF:
0.00237
Gnomad ASJ exome
AF:
0.00318
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.0195
Gnomad NFE exome
AF:
0.0113
Gnomad OTH exome
AF:
0.00847
GnomAD4 exome
AF:
0.0103
AC:
15025
AN:
1461884
Hom.:
118
Cov.:
31
AF XY:
0.0100
AC XY:
7297
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00164
Gnomad4 AMR exome
AF:
0.00244
Gnomad4 ASJ exome
AF:
0.00302
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000197
Gnomad4 FIN exome
AF:
0.0215
Gnomad4 NFE exome
AF:
0.0118
Gnomad4 OTH exome
AF:
0.00798
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00820
AC:
1247
AN:
152078
Hom.:
12
Cov.:
31
AF XY:
0.00822
AC XY:
611
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00164
Gnomad4 AMR
AF:
0.00190
Gnomad4 ASJ
AF:
0.00260
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000209
Gnomad4 FIN
AF:
0.0221
Gnomad4 NFE
AF:
0.0132
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00857
Hom.:
4
Bravo
AF:
0.00599
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0116
EpiControl
AF:
0.00942

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2023FOXN3: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
7.4
Dann
Benign
0.59
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs45535535; hg19: chr14-89629001; COSMIC: COSV99728009; COSMIC: COSV99728009; API